两种含铋四联方案治疗幽门螺杆菌感染根除后复发疗效及其影响因素

Two bismuth-containing quadruple regimens on treatment of recurrent Helicobacter pylori infection and the influencing factors

目的评价两种含铋四联疗法对幽门螺杆菌感染根除后复发治疗的有效性、安全性及影响因素。方法应用前瞻性、随机对照研究的方法,将清华大学玉泉医院(清华大学中西医结合医院)2017年3月至2020年9月收治的幽门螺杆菌感染根治后复发的95例患者应用随机信封法,分为研究组(45例)和对照组(50例),其中伴有萎缩性胃炎者分别为31例和28例。分别按照以莫西沙星为基础的含铋四联(胶体果胶铋200 mg、2次/d+雷贝拉唑10 mg、2次/d+阿莫西林1.0 g、2次/d+莫西沙星0.4 g、1次/d)和以甲硝唑为基础的含铋四联方案(胶体果胶铋200 mg、2次/d+雷贝拉唑10 mg、2次/d+阿莫西林1.0 g、2次/d+甲硝唑0.4 g、3次/d)均治疗2周。治疗结束4~8周,两组患者行13C尿素呼气试验。采用卡方检验分析幽门螺杆菌根除率、伴有萎缩性胃炎患者的根治率以及治疗后4周药物不良反应发生率。采用单因素分析和多因素Logistic回归分析筛选影响幽门螺杆菌感染根除后复发治疗的影响因素。结果研究组45例患者完成复发后治疗,37例患者幽门螺杆菌感染根除成功,意向性治疗分析(ITT)根治率和符合方案(PP)根治率分别为82.22%(37/45)和94.87%(37/39)。对照组50例患者完成复发后治疗,42例根除成功,ITT和PP根治率分别为82.22%(42/50)和87.5%(42/48)。两组患者ITT根治率(χ^(2)=0.783、P=0.800)和PP根治率(χ^(2)=1.551、P=0.297)差异均无统计学意义。研究组和对照组不良反应发生率分别为8.0%(4/45)和12%(6/50),差异无统计学意义(χ^(2)=0.243、P=0.744)。研究组中伴有萎缩性胃炎患者再次治疗后ITT根治率(96.77%vs.75.85%)和PP根治率(96.77%vs.78.57%)显著优于对照组中伴有萎缩性胃炎患者,差异有统计学意义(χ^(2)=5.670、P=0.017,χ^(2)=4.662、P=0.031)。单因素分析显示,不同药物依从性(服药率≥90%和<90%)、患者ITT根治率(91.57%vs.25.00%)和PP根治率(93.83%vs.27.27%)差异均有统计学意义(χ^(2)=28.59、P<0.001,χ^(2)=8.139、P=0.004)。而不同年龄、性别、吸烟、饮酒、是否伴有萎缩性胃炎、是否伴有消化不良、合并糖尿病、合并高血压、DOB值、根治药物等的患者ITT根治率和PP根治率差异均无统计学意义(P均>0.05)。多因素Logistic分析显示,药物依从性为幽门螺杆菌感染根除后复发根治疗效的影响因素(OR=0.035、95%CI:0.007~0.199、P<0.001)。结论以莫西沙星为基础的含铋四联疗法和以甲硝唑为基础的含铋四联疗法均可作为幽门螺杆菌感染复发患者治疗方案;两种方案的不良反应发生率相当。药物依从性为影响幽门螺杆菌感染复发根治疗效的独立影响因素。

Objective To evaluate the efficacy,safety and influencing factors of two bismuthcontaining quadruple therapies in the treatment of recurrent Helicobacter pylori(H.pylor)infection.Metheds Total of 95 patients with H.pylor recurrence infection from March 2017 to October 2020 in Tsinghua University Yuquan Hospital(Tsinghua University Hospital of Integrated Traditional Chinese and Western Medicine)were divided into experimental group(45 cases)and control group(50 cases)by ramdom envelope method,and there were 31 cases and 28 cases with atrophic gastritis in experimental group and control group,respectively.The experimental group were treated with colloidal bismuth pectin(200 mg,twice a day)+rabeprazole(10 mg,twice a day)+amoxicillin(1000 mg,twice a day)+moxifloxacin(0.4 mg,once a day).The control group were treated with bismuth pectin(200 mg,twice a day)+rabeprazole(10 mg,twice a day)+amoxicillin(1000 mg,twice a day)+metronidazole(0.4 mg,three times a day).All patients of the two groups were treated for 2 weeks.Then 13C urease breath test were performed on cases in both groups after 4-8 weeks.The eradication rate of recurrent H.pylor,eradication rate of cases with atrophic gastritis and the incidence of adverse drug reactions in 4 weeks after treatment were evaluated by Chi-square test.The risk factors for recurrent treatment failure of H.pylor were analyzed by Univariate and multivariate Logistic regression analysis.Results In experimental group,45 cases completed the treatment after relapse,among them,37 cases with H.pylor infection successfully eradicated,the eradication rates of intention-to-treat analysis(ITT)and per-protocol(PP)were 82.22%(37/45)and 94.87%(37/39),respectively.In control group,50 cases completed the treatment after relapse,among them,42 cases with H.pylor infection successfully eradicated,the eradication rates of ITT and PP were 82.22%(42/50)and 87.5%(42/48),respectively.There were no significant differences between the two groups for the eradication rates of ITT(χ^(2)=0.783,P=0.800)and PP(χ^(2)=1.551,P=0.297).The incidences of adverse reactions of experimental group and control group were 8.0%(4/45)and 12%(6/50),respectively,with no significant difference(χ^(2)=0.243,P=0.744).The eradication rates of ITT(96.77%vs.75.85%)and PP(96.77%vs.78.57%)after retreatment of patients complicated with atrophic gastritis in experimental group were significantly different from those of the control group(χ^(2)=5.670,P=0.017;χ^(2)=4.662,P=0.031).Univariate analysis showed that the eradication rates of ITT(91.57%vs.25.00%)and PP(93.83%vs.27.27%)between patients with different drug dependence(rate of taking medication≥90%and<90%)were significantly different(χ^(2)=28.59,P<0.001;χ^(2)=8.138,P=0.004).However,there was no significant difference for the eradication rates of ITT and PP between patients with different factors,such as age,sex,smoking,alcohol consumption,dyspepsia,dyspepsia,diabetes,hypertension,DOB value and radical drugs(all P>0.05).Multivariate Logistic analysis showed that drug dependence was a factor influencing the recurrent curative efficacy after the eradication of H.pylori infection(OR=0.035,95%CI:0.007-0.199,P<0.001).Conclusions Both moxifloxacin based bismuth-containing quadruple therapy and metronidazole based bismuth-containing quadruple therapy could be used to treat patients with recurrent H.pylor infection;with similar incidence of adverse reactions.Drug compliance was an independent influencing factor for the efficacy of radical treatment for recurrence of H.pylor infection.